Dopamine is a neurotransmitter which participates in a variety of different functions mediated by the nervous system, including vision, movement, and behavior. See generally Cooper, J. et al., The Biochemical Basis of Neuropharmacology, 161-195 (Oxford University Press, NY 3d Ed. 1978). The diverse physiological actions of dopamine are in turn mediated by its interaction with two basic types of G protein-coupled receptors: D.sub.1 and D.sub.2, which respectively stimulate and inhibit the enzyme adenylyl cyclase. Kebabian, J. and Calne, D., Nature 277, 93-96 (1979). Alterations in the number or activity of these receptors may be a contributory factor in disease states such as Parkinson's disease (a movement disorder) and schizophrenia (a behavioral disorder).
A great deal of information has accumulated on the biochemistry of the D.sub.1 - and D.sub.2 - dopamine receptors, and methods have been developed to solubilize and purify these receptor proteins. See Senogles, S. et al., Affinity Chromatography of the Anterior Pituitary D.sub.2 Dopamine Receptor, Biochemistry 25, 749-753 (1986); Senogles, S. et al., Purification and Characterization of the D.sub.2 Dopamine Receptor from Bovine Anterior Pituitary, J. Biol. Chem. 263, 18996-19002 (1988); Gingrich, J. et al., Affinity Chromatography of the D.sub.1 Dopamine Receptor from Rat Corpus Striatum, Biochemistry 27, 3907-3912 (1988); Gingrich, J. et al., Complete Purification of the D.sub.1 Dopamine Receptor from Rat Striatum (in press). The D.sub.1 dopamine receptor in several tissues appears to be a glycosylated membrane protein of about 72 kDa. Amlaiky, N. et al., Mol. Pharmacol. 31, 129-134 (1987); Ninik, H. et al., Biochemistry 27, 7594-7599 (1988). The D.sub.2 receptor has been suggested to have a higher molecular weight of about M.sub.r 90-150 kDa. Amlaiky, N. and Caron, M., J. Biol. Chem. 260, 1983-1986 (1985); Amlaiky, N. and Caron, M., J. Neurochem. 47, 196-204 (1986); Jarvie, K. et al., Mol. Pharmacol. 34, 91-97 (1988).
The cloning of the cDNA for a rat D.sub.2 dopamine receptor has recently been reported. See Bunzow, J. et al., Nature 336, 783-787 (1988); see also Civelli, O. et al., PCT Appln. WO 90/05780. This clone was obtained while probing for opiate receptors using the techniques of low stringency hybridization with the .beta..sub.2 -Adrenergic receptor cDNA. Ligand binding studies of this receptor, expressed in a mouse cell line, indicate that it binds ligands with appropriate D.sub.2 specificity. No clone for the D.sub.1 -dopamine receptor has yet been reported in the literature.